Synthesis and phosphodiesterase 5 inhibitory activity of new sildenafil analogues containing a phosphonate group in the 5′-sulfonamide moiety of phenyl ring

Dae Kee Kim, Ju Young Lee, Hyun Ju Park, Khac Minh Thai

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Synthesis of new sildenafil analogues containing a phosphonate group in the 5-sulfonamide moiety of the phenyl ring, 12a-e, 13a-d, and 14a-d, and evaluation of their in vitro PDE5 inhibitory activity are disclosed. Enzyme assays revealed that maximum 10-fold increase in PDE5 inhibitory activity, compared with sildenafil, was achieved by introducing a phosphonate group in the 5-sulfonamide moiety. Docking model of (PDE5: 12d) complex shows that the PDE5-bound conformation of 12d matches completely with that of sildenafil, while 12d is partially overlapped with cGMP with ethyl phosphonate group of 12d superimposed onto the cyclic phosphate group of cGMP.

Original languageEnglish
Pages (from-to)2099-2103
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number9
DOIs
StatePublished - 3 May 2004

Keywords

  • PDE5 inhibitor

Fingerprint

Dive into the research topics of 'Synthesis and phosphodiesterase 5 inhibitory activity of new sildenafil analogues containing a phosphonate group in the 5′-sulfonamide moiety of phenyl ring'. Together they form a unique fingerprint.

Cite this